A traditional Chinese medicine composition for treating glaucoma and a preparation method thereof

Abstract

This invention relates to the field of traditional Chinese medicine (TCM) technology. The invention provides a TCM composition for treating glaucoma and its preparation method, comprising the following components in parts by weight: 18-28 parts of Cassia seed, 12-18 parts of Lycium fruit, 12-18 parts of Eriocaulon buergerianum, 10-15 parts of vinegar-processed Cyperus rotundus, 10-15 parts of mulberry leaf, 10-15 parts of Ligusticum chuanxiong, 8-12 parts of Polyporus umbellatus, 5-8 parts of Pueraria lobata, 5-8 parts of Akebia quinata, 3-5 parts of Curcuma longa, 3-5 parts of Indigo naturalis, and 2-4 parts of prepared licorice root. The TCM composition of this invention has a strong effect in lowering intraocular pressure, improving retinal blood supply, and preventing optic nerve atrophy caused by glaucoma; simultaneously, the processing method maximizes the retention of the active pharmaceutical ingredients. Furthermore, the technical solution of this invention achieves a dual improvement in efficacy and safety, and also reduces the recurrence rate and side effects.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating glaucoma and its preparation method. Background Technology

[0002] Glaucoma is the leading cause of irreversible blindness worldwide. Its core pathological mechanism involves pathologically elevated intraocular pressure leading to insufficient perfusion of the central retinal artery and apoptosis of optic ganglion cells, ultimately resulting in optic nerve atrophy and visual field defects. Modern medicine's treatment of glaucoma primarily focuses on controlling intraocular pressure, commonly using medications, lasers, or surgery. However, single-drug therapy has limited effectiveness in lowering intraocular pressure, and combined medications can easily cause side effects such as conjunctival congestion, corneal dryness, and abnormal heart rate. Furthermore, these methods only control intraocular pressure and cannot fundamentally improve ocular microcirculation or protect the optic nerve. Long-term medication use can easily lead to drug resistance and side effects. Surgical treatment is invasive, with a long postoperative recovery period, and some patients still experience poor visual recovery after surgery.

[0003] Traditional Chinese medicine (TCM) believes that the occurrence of glaucoma (belonging to the categories of "green wind cataract" and "glaucoma internal cataract") is closely related to emotional imbalance, liver qi stagnation, excessive liver fire, obstruction of the optic nerve's internal organs, and stagnation of optic nerve fluid. Simultaneously, liver and kidney deficiency and insufficient qi and blood can exacerbate optic nerve damage. TCM treatment of glaucoma has the advantages of holistic regulation, fewer side effects, and protection of the optic nerve. However, current TCM treatment plans often employ single-herb prescriptions based on syndrome differentiation, or the formulation is not precise enough, resulting in limited efficacy, long treatment courses, and weak targeting. Some prescriptions can only relieve symptoms and cannot address both the symptoms and the root cause, failing to meet clinical treatment needs. Furthermore, there are problems such as low retention rate of active ingredients, unstable efficacy, and insufficient technological content, making it difficult to simultaneously achieve the multiple goals of effectively lowering intraocular pressure, improving retinal blood supply, protecting the optic nerve, and reducing recurrence rates. Therefore, developing a TCM composition for glaucoma treatment with advanced technology, sufficient retention of active ingredients, definite efficacy, and high safety has become an urgent technical problem to be solved in the field of TCM. Summary of the Invention

[0004] The purpose of this invention is to provide a traditional Chinese medicine composition for treating glaucoma, which can significantly reduce intraocular pressure, improve retinal blood supply, prevent optic nerve atrophy caused by glaucoma, achieve a dual improvement in efficacy and safety, and reduce recurrence rate and side effects.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a traditional Chinese medicine composition for treating glaucoma, comprising the following components in parts by weight: 18-28 parts of cassia seed, 12-18 parts of wolfberry fruit, 12-18 parts of cottongrass, 10-15 parts of vinegar-processed cyperus rhizome, 10-15 parts of mulberry leaf, 10-15 parts of chuanxiong rhizome, 8-12 parts of polyporus umbellatus, 5-8 parts of kudzu root, 5-8 parts of akebia stem, 3-5 parts of turmeric, 3-5 parts of indigo naturalis, and 2-4 parts of prepared licorice root.

[0006] This invention provides a method for preparing the aforementioned traditional Chinese medicine composition, comprising the following steps: (1) Crush cassia seed, wolfberry, vinegar-processed cyperus rhizome, mulberry leaf and roasted licorice root, mix them together, add water and decoct, filter to obtain filtrate 1; (2) After slicing Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata, mix them together, extract with ethanol, and filter to obtain filtrate 2; (3) Mix the obtained filtrate 1, filtrate 2, indigo with the crushed akebia and turmeric, and concentrate to obtain the final product.

[0007] Preferably, after crushing in step (1), the material is sieved through a screen with a mesh size of 40-60.

[0008] Preferably, the amount of water added in step (1) is 8-12 times the total mass of cassia seed, wolfberry, vinegar-processed cyperus rhizome, mulberry leaf, and roasted licorice root.

[0009] Preferably, the decocting time in step (1) is 50-70 min / time, and the number of decocting times is 2-3 times.

[0010] Preferably, the volume-to-mass ratio of ethanol to the total mass of Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata in step (2) is (10-20) mL:(1-3) g.

[0011] Preferably, the extraction time in step (2) is 60-100 min / time, and the number of extractions is 2-3 times.

[0012] The present invention also provides the application of the traditional Chinese medicine composition in the preparation of drugs for treating glaucoma.

[0013] Preferably, the dosage form of the glaucoma treatment drug includes granules, capsules, or oral liquid.

[0014] By adopting the above technical solution, the present invention has the following beneficial effects: This invention, based on the principles of traditional Chinese medicine (TCM) syndrome differentiation and treatment, combined with modern pharmacological research, optimizes the formulation and compatibility of Chinese herbal medicines, resulting in a precisely formulated and synergistically effective composition. This composition addresses the root causes of visceral imbalances, balances Qi and blood, clears meridians, clears liver fire, tonifies the liver and kidneys, promotes blood circulation, removes blood stasis, and improves vision by eliminating dampness. Furthermore, this herbal composition exhibits a strong effect in lowering intraocular pressure, improving retinal blood supply, and preventing optic nerve atrophy caused by glaucoma. It achieves both enhanced efficacy and safety while reducing recurrence rates and side effects.

[0015] The method of this invention is designed with graded extraction processes based on the solubility of components of different medicinal flavors. Combined with low-temperature purification and other technologies, it maximizes the retention of active ingredients in the medicine. Compared with simple powder mixing, it has higher technical content and the process is stable and suitable for industrial production. Detailed Implementation

[0016] This invention provides a traditional Chinese medicine composition for treating glaucoma, comprising the following components: cassia seed, wolfberry fruit, cottonberry, vinegar-processed cyperus rhizome, mulberry leaf, chuanxiong rhizome, polyporus umbellatus, kudzu root, akebia stem, turmeric, indigo naturalis, and prepared licorice root.

[0017] In this invention, the weight percentage of Cassia tora seeds is preferably 18-28 parts, more preferably 20-26 parts, and even more preferably 25 parts; the weight percentage of Lycium barbarum seeds is preferably 12-18 parts, more preferably 13-17 parts, and even more preferably 16 parts; the weight percentage of Eriocaulon buergerianum is preferably 12-18 parts, more preferably 13-17 parts, and even more preferably 15 parts; the weight percentage of Cyperus rotundus (processed with vinegar) is preferably 10-15 parts, more preferably 11-14 parts, and even more preferably 13 parts; the weight percentage of mulberry leaves is preferably 10-15 parts, more preferably 11-14 parts, and even more preferably 12 parts; the weight percentage of Ligusticum chuanxiong is preferably 10-15 parts, more preferably 11-14 parts, and even more preferably 15 parts. The preferred weight percentage of the first step is 12 parts; the preferred weight percentage of the *Polyporus umbellatus* is 8-12 parts, more preferably 9-11 parts, and even more preferably 10 parts; the preferred weight percentage of the *Pueraria lobata* is 5-8 parts, more preferably 6-7.5 parts, and even more preferably 7 parts; the preferred weight percentage of the *Akebia trifoliata* is 5-8 parts, more preferably 5.5-7 parts, and even more preferably 6 parts; the preferred weight percentage of the *Curcuma longa* is 3-5 parts, more preferably 3.5-4.8 parts, and even more preferably 4.5 parts; the preferred weight percentage of the *Indigofera tinctoria* is 3-5 parts, more preferably 3.5-4.5 parts, and even more preferably 4 parts; the preferred weight percentage of the *Glycyrrhiza uralensis* (processed) is 2-4 parts, more preferably 2.5-3.5 parts, and even more preferably 3 parts.

[0018] In this invention, the cassia seed is sweet, bitter, and salty in taste, slightly cold in nature, and enters the liver and large intestine meridians. It clears liver heat and improves vision, moistens the intestines and promotes bowel movements, assisting in clearing liver fire and improving vision, while also moistening the intestines and promoting bowel movements to prevent constipation from causing increased intraocular pressure. The chuanxiong rhizome in this invention can help improve ocular microcirculation and relieve headaches caused by increased pressure; the poria cocos improves the body's fluid metabolism by promoting diuresis and helps reduce ocular tension; the mulberry leaf contains flavonoids (such as rutin and quercetin), polysaccharides, γ-aminobutyric acid (GABA), etc., which can reduce oxidative stress damage to ocular tissues and relax the ciliary muscle. The synergistic combination of these four traditional Chinese medicine ingredients can better improve ocular microcirculation, reduce intraocular pressure, and relieve eye swelling and pain.

[0019] In this invention, *Eriocaulon buergerianum* is sweet and pungent in taste, neutral in nature, and enters the liver and lung meridians; its active ingredients are ethionin and flavonoids, which can dispel wind-heat, improve eyesight and remove corneal opacity, enhance the sensitivity of retinal photoreceptor cells, improve visual field defects in glaucoma patients, and synergistically relieve symptoms of dry and itchy eyes. *Lycium barbarum* replenishes the essence and blood of the liver and kidneys to nourish the eyes; *Cyperus rotundus* is pungent, slightly bitter, and slightly sweet in taste, neutral in nature, and enters the liver, spleen, and triple burner meridians, which can soothe the liver and relieve depression, promote qi circulation and relieve pain, and invigorate blood circulation, relieving eye distension and pain caused by liver qi stagnation, clearing the eye meridians, and improving eye obstruction; *Pueraria lobata* relieves muscle tension and fever, raises yang and lifts prolapse; *Curcuma longa* promotes qi circulation, relieves depression, invigorates blood circulation and relieves pain. Several ingredients work synergistically to enhance the effect of lowering intraocular pressure. At the same time, through the synergistic effect of promoting blood circulation and unblocking collaterals, they improve the blood flow perfusion of the central retinal artery, solve the problem of optic nerve ischemia caused by elevated intraocular pressure, achieve both symptomatic and root cause treatment, solve the pathogenesis of glaucoma "elevated intraocular pressure as the symptom, and liver and kidney yin deficiency and optic nerve malnourishment as the root cause", and reduce the recurrence rate.

[0020] In this invention, the indigo naturalis is a dried powder, lumps, or granules obtained by processing the leaves or stems of *Strobilanthes cusia* (Acanthaceae), *Polygonum tinctorium* (Polygonaceae), and *Isatis tinctoria* (Brassicaceae). The indigo naturalis contains indigo, indirubin, and other components, which can inhibit various bacteria and viruses; it has the effects of clearing heat and detoxifying, cooling blood and eliminating spots, relieving sore throat and swelling, and clearing corneal opacity and improving vision; it can synergistically regulate microcirculation with flavonoids; indigo naturalis can help suppress liver yang and is effective for conjunctivitis or eyelid congestion caused by staying up late. Synergistically with *Akebia trifoliata*, it clears liver fire, promotes diuresis, and unblocks aqueous humor, providing a certain adjunctive therapeutic effect for glaucoma.

[0021] In this invention, the preparation method of the indigo is as follows: (1) Take the leaves or stems of the plants Acanthaceae, Polygonaceae, or Brassicaceae, and extract them in hot water. Filter to remove the leaf residue and obtain the filtrate; (2) Add an acid solution to the filtrate for hydrolysis. After hydrolysis, a hydrolyzed mixture is obtained; (3) Add an alkaline solution to adjust the pH of the hydrolyzed mixture to 6-8, let it stand and discard the supernatant, take the precipitate, wash it until neutral, and dry it to obtain indigo. The preferred temperature of the hot water in this invention is 60-80℃, more preferably 65-75℃, and even more preferably 70℃; the preferred volume-to-mass ratio of the hot water to the fresh leaves is (10-20) mL:1g, more preferably (12-18) mL:1g, and even more preferably 15 mL:1g; the preferred extraction time is 15-25 min / time, more preferably 18-22 min / time, and even more preferably 20 min / time; the preferred number of extractions is 2-3 times, more preferably 3 times. The preferred acid solution in this invention is acetic acid or hydrochloric acid, more preferably hydrochloric acid; the preferred alkaline solution is sodium hydroxide or ammonia, more preferably sodium hydroxide. The moisture content of the indigo naturalis in this invention does not exceed 7%.

[0022] In this invention, the prepared licorice root harmonizes the various herbs, which can alleviate the slight irritation of the blood-activating herbs in the whole formula, reduce the risk of congestion of the eye mucosa, and at the same time enhance the stability of the active ingredients of each herb, thereby improving the overall efficacy of the formula.

[0023] The present invention also provides a method for preparing the traditional Chinese medicine composition, comprising the following steps: (1) Crush cassia seed, wolfberry, vinegar-processed cyperus rhizome, mulberry leaf and roasted licorice root, mix them together, add water and decoct, filter to obtain filtrate 1; (2) After slicing Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata, mix them together, extract with ethanol, and filter to obtain filtrate 2; (3) Mix the obtained filtrate 1, filtrate 2, indigo with the crushed akebia and turmeric, and concentrate to obtain the final product.

[0024] In this invention, it is preferred to pretreat each component of the traditional Chinese medicine to remove impurities and dust, wash and dry them. The drying process is preferably hot air drying at 40-45℃ until the moisture content is ≤8.0%.

[0025] In this invention, cassia seeds, wolfberries, vinegar-processed cyperus rhizome, mulberry leaves, and prepared licorice root are pulverized separately and then sieved through a screen. The sieve residue is collected for later use. The mesh size of the screen used in this invention is preferably 40-60 mesh, more preferably 45-55 mesh, and even more preferably 50 mesh. The purpose of pulverization is to increase the contact area between the medicinal materials and the solvent, thereby improving extraction efficiency.

[0026] In this invention, the amount of water added is preferably 8-12 times the total mass of cassia seed, wolfberry, vinegar-processed cyperus rhizome, mulberry leaf, and prepared licorice root, more preferably 9-11 times, and even more preferably 10 times.

[0027] In this invention, the decoction time is preferably 50-70 min / time, more preferably 55-65 min / time, and even more preferably 60 min / time; the number of decoctions is preferably 2-3 times, more preferably 2 times. After each decoction, the mixture is filtered to separate the dregs, the filtrate is collected, and then the filtrates are combined to finally obtain filtrate 1.

[0028] In this invention, *Eriocaulon buergerianum*, *Polyporus umbellatus*, *Ligusticum chuanxiong*, and *Pueraria lobata* are sliced ​​and then mixed. The thickness of the slices is preferably 1-3 mm, more preferably 1.5-2.5 mm, and even more preferably 2 mm. The purpose of slicing is to increase the contact area between the medicinal materials and the solvent, thereby improving the extraction efficiency.

[0029] In this invention, the preferred volume-to-mass ratio of ethanol to the total mass of Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong, and Pueraria lobata is (10-20) mL:(1-3) g, more preferably (12-18) mL:(1.2-2.5) g, and even more preferably 15 mL:2 g. The preferred volume concentration of ethanol in this invention is 75-85%, more preferably 80%.

[0030] In this invention, the extraction method is preferably reflux extraction, and the heating temperature is preferably 60-65℃, more preferably 61-64℃, and even more preferably 62℃; the extraction time is preferably 60-100 min / time, more preferably 70-90 min / time, and even more preferably 80 min / time; the number of extractions is preferably 2-3 times, and even more preferably 2 times. After each extraction, the residue is filtered to separate the medicinal residue, the filtrate is collected, and then the filtrates are combined to finally obtain filtrate 2.

[0031] In this invention, the akebia quinata and turmeric are crushed and sieved, and the sieve material is collected. The mesh size of the sieve is preferably 40-60 mesh, more preferably 45-55 mesh, and even more preferably 50 mesh.

[0032] In this invention, filtrate 1, filtrate 2, indigo naturalis, and pulverized akebia stem and turmeric are mixed evenly. Then, anhydrous ethanol is added to bring the ethanol volume fraction of the system to 25%-30%. After stirring, the mixture is refrigerated and allowed to stand for a period of time. After filtration, the filtrate is concentrated under reduced pressure until no alcohol odor remains. Then, further concentration is carried out to obtain an extract. The stirring time is preferably 15-20 min, more preferably 16-19 min, and even more preferably 18 min; the refrigeration temperature is preferably 4-6℃; the refrigeration time is preferably 18-24 h, more preferably 19-23 h, and even more preferably 22 h; the reduced pressure concentration temperature is preferably 55-60℃, more preferably 57-59℃, and even more preferably 58℃; the relative density of the extract is preferably 1.18-1.30. The operation described in this invention removes impurities such as tannins, macromolecular polysaccharides, and proteins from the extract through ethanol precipitation, thereby improving the purity of the extract and avoiding eye irritation caused by impurities. Refrigeration at 4-6°C can reduce the loss of active ingredients during the purification process.

[0033] The present invention also provides the application of the traditional Chinese medicine composition in the preparation of drugs for treating glaucoma.

[0034] In this invention, the dosage form of the glaucoma treatment drug includes granules, capsules, or oral liquids.

[0035] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0036] Example 1

[0037] A traditional Chinese medicine composition for treating glaucoma, comprising the following components: 25 parts cassia seed, 16 parts wolfberry, 15 parts cottongrass, 13 parts vinegar-processed cyperus rhizome, 12 parts mulberry leaf, 12 parts chuanxiong rhizome, 10 parts polyporus umbellatus, 7 parts kudzu root, 6 parts akebia stem, 4.5 parts turmeric, 4 parts indigo naturalis, and 3 parts prepared licorice root.

[0038] Example 2

[0039] A traditional Chinese medicine composition for treating glaucoma, comprising the following components: 18 parts of cassia seed, 12 parts of wolfberry, 18 parts of cottongrass, 15 parts of vinegar-processed cyperus rhizome, 10 parts of mulberry leaf, 15 parts of chuanxiong rhizome, 8 parts of polyporus umbellatus, 8 parts of kudzu root, 8 parts of akebia stem, 3 parts of turmeric, 5 parts of indigo naturalis, and 2 parts of prepared licorice root.

[0040] Example 3

[0041] A traditional Chinese medicine composition for treating glaucoma, comprising the following components: 28 parts of cassia seed, 18 parts of wolfberry, 12 parts of cottongrass, 10 parts of vinegar-processed cyperus rhizome, 15 parts of mulberry leaf, 10 parts of chuanxiong rhizome, 12 parts of polyporus umbellatus, 5 parts of kudzu root, 5 parts of akebia stem, 5 parts of turmeric, 3 parts of indigo naturalis, and 4 parts of prepared licorice root.

[0042] Example 4

[0043] The preparation method of the traditional Chinese medicine composition described in Example 1 includes the following steps: (1) Remove impurities and dust from each Chinese herbal medicine component, wash it, and dry it with hot air at 45°C until the moisture content is ≤8.0%; (2) Crush cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice separately and pass them through a 50-mesh sieve. Collect the sieve residue and mix it evenly. Add water equal to 10 times the total mass of cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice and decoct for 60 minutes each time, twice. After each decoction, filter to separate the dregs, collect the filtrate, and then combine the filtrates to finally obtain filtrate 1. (3) Cut the herbs Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata into 2 mm slices and mix them together. Add 80% ethanol at a volume ratio of 15 mL: 2 g to the total mass of Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata. Heat and reflux at 62℃ for 80 min / time, and extract twice. After each extraction, filter to separate the residue, collect the filtrate, and then combine the filtrates to obtain filtrate 2. (4) Take the leaves or stems of *Isatis tinctoria* (Acanthaceae), *Polygonum tinctoria* (Polygonaceae), or *Isatis tinctoria* (Brassicaceae), mix the corresponding fresh leaves with 70℃ hot water at a volume ratio of 15mL:1g and extract for 20min / time, for 3 times. After each extraction, filter to separate the leaf residue, collect the filtrate, and then combine the filtrates. Add 2% hydrochloric acid to the filtrate and hydrolyze for 40min. After hydrolysis, obtain a hydrolyzed mixture. Then add 2% sodium hydroxide to adjust the pH of the hydrolyzed mixture to 6-8, let it stand and discard the supernatant, take the precipitate, wash until neutral, and dry to obtain indigo naturalis. The moisture content of the indigo naturalis shall not exceed 7%. (5) After crushing the akebia and turmeric, pass them through a 50-mesh sieve and collect the sieve residue. Then, mix the obtained filtrate 1, filtrate 2, indigo with the crushed akebia and turmeric evenly, add anhydrous ethanol to make the ethanol volume fraction of the system reach 25%, stir for 18 min, refrigerate at 4℃ for 22 h, filter, take the filtrate and concentrate under reduced pressure at 58℃ until there is no alcohol smell, and continue to concentrate to an extract with a relative density of 1.25.

[0044] Example 5

[0045] The preparation method of the traditional Chinese medicine composition described in Example 1 includes the following steps: (1) Remove impurities and dust from each Chinese herbal medicine component, wash it, and dry it with hot air at 40°C until the moisture content is ≤8.0%; (2) Crush cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice into powder, pass them through a 40-mesh sieve, collect the sieve residue and mix them evenly. Add water equal to 8 times the total mass of cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice and decoct for 50 minutes each time, twice. After each decoction, filter to separate the dregs, collect the filtrate, and then combine the filtrates to finally obtain filtrate 1. (3) Cut the herbs Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata into 2 mm slices and mix them together. Add 75% ethanol at a volume ratio of 20 mL:1 g to the total mass of Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata. Heat and reflux at 60 °C for 100 min / time, and extract twice. After each extraction, filter to separate the residue, collect the filtrate, and then combine the filtrates to obtain filtrate 2. (4) Take the leaves or stems of *Isatis tinctoria* (Acanthaceae), *Polygonum tinctoria* (Polygonaceae), or *Isatis tinctoria* (Brassicaceae), mix the corresponding fresh leaves with 70℃ hot water at a volume ratio of 10mL:1g and extract for 15min / time, for 3 times. After each extraction, filter to separate the leaf residue, collect the filtrate, and then combine the filtrates. Add 2% hydrochloric acid to the filtrate and hydrolyze for 40min. After hydrolysis, obtain a hydrolyzed mixture. Then add 2% sodium hydroxide to adjust the pH of the hydrolyzed mixture to 6-8, let it stand and discard the supernatant, take the precipitate, wash until neutral, and dry to obtain indigo naturalis. The moisture content of the indigo naturalis shall not exceed 7%. (5) After crushing the Akebia quinata and Curcuma longa, pass them through a 40-mesh sieve and collect the sieve residue. Then, mix the obtained filtrate 1, filtrate 2, and Indigo naturalis with the crushed Akebia quinata and Curcuma longa evenly. Add anhydrous ethanol to make the ethanol volume fraction of the system reach 25%. Stir for 20 minutes, refrigerate at 6°C and let stand for 24 hours. Filter, take the filtrate and concentrate it under reduced pressure at 55°C until there is no alcohol smell. Continue to concentrate until the extract has a relative density of 1.30.

[0046] Example 6

[0047] The preparation method of the traditional Chinese medicine composition described in Example 1 includes the following steps: (1) Remove impurities and dust from each Chinese herbal medicine component, wash it, and dry it with hot air at 40°C until the moisture content is ≤8.0%; (2) Crush cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice into powder, pass them through a 60-mesh sieve, collect the sieve residue and mix them evenly. Add water equal to 12 times the total mass of cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice and decoct for 70 minutes each time, twice. After each decoction, filter to separate the dregs, collect the filtrate, and then combine the filtrates to finally obtain filtrate 1. (3) Cut the herbs Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata into 2 mm slices and mix them together. Add 85% ethanol at a volume ratio of 10 mL:1 g of ethanol to the total mass of Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata. Heat and reflux at 65°C for 60 min / time, and extract 3 times. After each extraction, filter to separate the residue, collect the filtrate, and then combine the filtrates to obtain filtrate 2. (4) Take the leaves or stems of *Isatis tinctoria* (Acanthaceae), *Polygonum tinctoria* (Polygonaceae), or *Isatis tinctoria* (Brassicaceae), mix the corresponding fresh leaves with 65℃ hot water at a volume ratio of 20mL:1g and extract, 25min / time, twice. After each extraction, filter to separate the leaf residue, collect the filtrate, and then combine the filtrates; add 2% hydrochloric acid to the filtrate for 40min to hydrolyze, and after hydrolysis, obtain a hydrolyzed mixture; then add 2% sodium hydroxide to adjust the pH of the hydrolyzed mixture to 6-8, let it stand and discard the supernatant, take the precipitate, wash until neutral, and dry to obtain indigo naturalis, the moisture content of the indigo naturalis shall not exceed 7%; (5) After crushing the Akebia quinata and Curcuma longa, pass them through a 60-mesh sieve and collect the sieve residue. Then, mix the obtained filtrate 1, filtrate 2, and Indigo naturalis with the crushed Akebia quinata and Curcuma longa evenly. Add anhydrous ethanol to make the ethanol volume fraction of the system reach 25%. Stir for 15 min, refrigerate at 6℃ and let stand for 18 h. Filter, take the filtrate and concentrate it under reduced pressure at 55℃ until there is no alcohol smell. Continue to concentrate until the extract has a relative density of 1.18.

[0048] Example 7

[0049] The preparation method of the traditional Chinese medicine composition described in Example 2 is as follows: (1) Remove impurities and dust from each Chinese herbal medicine component, wash it, and dry it with hot air at 45°C until the moisture content is ≤8.0%; (2) Crush cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice separately and pass them through a 50-mesh sieve. Collect the sieve residue and mix it evenly. Add water equal to 10 times the total mass of cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice and decoct for 60 minutes each time, twice. After each decoction, filter to separate the dregs, collect the filtrate, and then combine the filtrates to finally obtain filtrate 1. (3) Cut the herbs Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata into 2 mm slices and mix them together. Add 80% ethanol at a volume ratio of 15 mL: 2 g to the total mass of Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata. Heat and reflux at 62℃ for 80 min / time, and extract twice. After each extraction, filter to separate the residue, collect the filtrate, and then combine the filtrates to obtain filtrate 2. (4) Take the leaves or stems of *Isatis tinctoria* (Acanthaceae), *Polygonum tinctoria* (Polygonaceae), or *Isatis tinctoria* (Brassicaceae), mix the corresponding fresh leaves with 70℃ hot water at a volume ratio of 15mL:1g and extract for 20min / time, for 3 times. After each extraction, filter to separate the leaf residue, collect the filtrate, and then combine the filtrates. Add 2% hydrochloric acid to the filtrate and hydrolyze for 40min. After hydrolysis, obtain a hydrolyzed mixture. Then add 2% sodium hydroxide to adjust the pH of the hydrolyzed mixture to 6-8, let it stand and discard the supernatant, take the precipitate, wash until neutral, and dry to obtain indigo naturalis. The moisture content of the indigo naturalis shall not exceed 7%. (5) After crushing the akebia and turmeric, pass them through a 50-mesh sieve and collect the sieve residue. Then, mix the obtained filtrate 1, filtrate 2, indigo with the crushed akebia and turmeric evenly, add anhydrous ethanol to make the ethanol volume fraction of the system reach 25%, stir for 18 min, refrigerate at 4℃ for 22 h, filter, take the filtrate and concentrate under reduced pressure at 58℃ until there is no alcohol smell, and continue to concentrate to an extract with a relative density of 1.25.

[0050] Example 8

[0051] The preparation method of the traditional Chinese medicine composition described in Example 3 is as follows: (1) Remove impurities and dust from each Chinese herbal medicine component, wash it, and dry it with hot air at 45°C until the moisture content is ≤8.0%; (2) Crush cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice separately and pass them through a 50-mesh sieve. Collect the sieve residue and mix it evenly. Add water equal to 10 times the total mass of cassia seeds, wolfberries, vinegar-processed cyperus, mulberry leaves and prepared licorice and decoct for 60 minutes each time, twice. After each decoction, filter to separate the dregs, collect the filtrate, and then combine the filtrates to finally obtain filtrate 1. (3) Cut the herbs Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata into 2 mm slices and mix them together. Add 80% ethanol at a volume ratio of 15 mL: 2 g to the total mass of Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata. Heat and reflux at 62℃ for 80 min / time, and extract twice. After each extraction, filter to separate the residue, collect the filtrate, and then combine the filtrates to obtain filtrate 2. (4) Take the leaves or stems of *Isatis tinctoria* (Acanthaceae), *Polygonum tinctoria* (Polygonaceae), or *Isatis tinctoria* (Brassicaceae), mix the corresponding fresh leaves with 70℃ hot water at a volume ratio of 15mL:1g and extract for 20min / time, for 3 times. After each extraction, filter to separate the leaf residue, collect the filtrate, and then combine the filtrates. Add 2% hydrochloric acid to the filtrate and hydrolyze for 40min. After hydrolysis, obtain a hydrolyzed mixture. Then add 2% sodium hydroxide to adjust the pH of the hydrolyzed mixture to 6-8, let it stand and discard the supernatant, take the precipitate, wash until neutral, and dry to obtain indigo naturalis. The moisture content of the indigo naturalis shall not exceed 7%. (5) After crushing the akebia and turmeric, pass them through a 50-mesh sieve and collect the sieve residue. Then, mix the obtained filtrate 1, filtrate 2, indigo with the crushed akebia and turmeric evenly, add anhydrous ethanol to make the ethanol volume fraction of the system reach 25%, stir for 18 min, refrigerate at 4℃ for 22 h, filter, take the filtrate and concentrate under reduced pressure at 58℃ until there is no alcohol smell, and continue to concentrate to an extract with a relative density of 1.25.

[0052] Comparative Example 1

[0053] Similar to Example 4, only Indigo Naturalis, Akebia Stem, Curcuma longa, and step (4) are removed.

[0054] Comparative Example 2

[0055] Similar to Example 4, only the following ingredients were removed: Polyporus umbellatus, Ligusticum chuanxiong, Cyperus rotundus (processed with vinegar), and Morus alba.

[0056] Comparative Example 3

[0057] Similar to Example 4, except that "the herbs *Eriocaulon buergerianum*, *Polyporus umbellatus*, *Ligusticum chuanxiong*, and *Pueraria lobata* were cut into 2mm slices and mixed. 80% ethanol was added at a volume ratio of 15mL:2g, and the mixture was heated to reflux at 62°C for 80min / time, for two extractions. After each extraction, the mixture was filtered to separate the residue, and the filtrate was collected. The filtrates were then combined to obtain filtrate 2" was replaced with "the herbs *Eriocaulon buergerianum*, *Polyporus umbellatus*, *Ligusticum chuanxiong*, and *Pueraria lobata* were cut into 2mm slices and mixed. Water was added at a volume ratio of 15mL:2g, and the mixture was decocted at 62°C for 80min / time, for two extractions. After each decoction, the mixture was filtered to separate the residue, and the filtrate was collected. The filtrates were then combined to obtain filtrate 2".

[0058] Comparative Example 4

[0059] Similar to Example 4, except that "add anhydrous ethanol to make the ethanol volume fraction of the system reach 25%, stir for 18 min, refrigerate at 4°C for 22 h, filter, take the filtrate and concentrate under reduced pressure at 58°C until there is no alcohol odor, and continue to concentrate to an extract with a relative density of 1.25" is replaced with "concentrate to an extract with a relative density of 1.25".

[0060] Experimental Example 1: Ocular Cytotoxicity Test

[0061] Human corneal epithelial cells (HCEC, purchased from ATCC website) were selected as target tissue-associated cells for glaucoma and cultured in culture flasks. The flasks containing cells were placed in an incubator at 37°C, 5% CO2, and 80%-90% humidity. The medium was changed daily, and the cells were observed under an inverted microscope. Subculture was performed after 3-4 days, and the cells were used after reaching the logarithmic growth phase. DMEM / F-12 medium containing 10% fetal bovine serum and 10% antibiotic solution with high glucose was used as the culture medium.

[0062] Cells were spaced at 10 per well. 4 Cells were seeded into 96-well plates, PBS solution was added around each well, and the plates were incubated for 24 hours. The culture medium was then removed, and 100 μL of the traditional Chinese medicine composition prepared in Example 4 was added. An equal volume of culture medium was used as a blank control. After a certain incubation period, the waste liquid was removed, and the cells were washed with 200 μL of PBS. DMEM / F-12 medium containing 10 μL of MTT was then added, and the cells were incubated for 4 hours. The waste liquid was then discarded, and 120 μL of DMSO was added to each well. The plates were then incubated at 37°C and 5% CO2 for 10 minutes. The volume of the traditional Chinese medicine composition prepared in Example 4 was varied to 80 μL, 60 μL, 40 μL, and 20 μL to compare the effects of different dosage volumes on HCEC cells.

[0063] The OD value at 570 nm was measured using an enzyme-linked immunosorbent assay (ELISA) reader, and the cell viability was calculated.

[0064] Cell viability rate = OD of experimental group 570nm Value / Cell control group OD 570nm Value × 100%

[0065] Table 1. Cell viability rates in different treatment groups

[0066] As shown in Table 1, high drug volume has a certain degree of toxicity to HCEC cells, and the degree of cell damage gradually decreases as the drug volume decreases.

[0067] Experimental Example 2

[0068] Three hundred glaucoma patients were randomly selected, including 120 cases of acute angle-closure glaucoma and 180 cases of primary open-angle glaucoma. All patients presented with varying degrees of visual impairment, blurred vision, and eye pain, and all still retained light perception. Patients with severe liver or kidney dysfunction, pregnant women, breastfeeding women, those with a history of eye surgery, congenital eye diseases, allergies to any component of this composition, or other serious illnesses were excluded. All patients were randomly divided into six groups of 50 each: Example 4 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, and control group. There were no statistically significant differences in general characteristics such as gender, age, disease duration, and disease severity among the six groups. P (>0.05), making them comparable.

[0069] The control group received 0.5% timolol eye drops, 1-2 drops / eye, twice daily, for 3 consecutive months. The remaining groups received the traditional Chinese medicine preparations prepared in Example 4, Comparative Example 1, Comparative Example 2, Comparative Example 3, and Comparative Example 4, respectively (the extracts prepared in each group were dried, pulverized to a fine powder of 120 mesh, and filled into empty capsules, each capsule containing 0.6g), 2-3 capsules three times daily with warm water, for 3 consecutive months. (one)

[0071] The mean intraocular pressure (IOP) of the affected eye was measured before medication and at 2 and 12 weeks after medication. The results are shown in Table 2.

[0072] Table 2. Mean intraocular pressure before and after medication in different groups of patients.

[0073] The results showed that patients using the product described in this invention experienced the highest reduction in average intraocular pressure in their affected eyes, and the effect was also better than that of the control group. (two)

[0075] Before and 12 weeks after medication, color Doppler ultrasound was used to measure the peak systolic velocity (PSV) and end-diastolic velocity (EDV) of the central retinal artery, and the improvement rate of blood perfusion was calculated.

[0076] PSV improvement rate (%) = (PSV at 12 weeks of medication - PSV before medication) / PSV before medication × 100%

[0077] EDV improvement rate (%) = (EDV at 12 weeks of medication - EDV before medication) / EDV before medication × 100%

[0078] Table 3. Improvement of blood perfusion in different groups before and after 12 weeks of medication.

[0079] As can be seen from Table 3, after using the traditional Chinese medicine composition described in this invention, the peak systolic velocity and end-diastolic velocity of the central retinal artery of patients were significantly improved, indicating that the retinal blood perfusion and blood supply can be significantly improved. (three)

[0081] Overall efficacy evaluation criteria: ① Marked effect: Intraocular pressure decreased by ≥10 mmHg and returned to normal, central retinal artery blood flow perfusion significantly improved (PSV and EDV increased by ≥30%), optic ganglion cell layer thickness increased by ≥20%, and clinical symptoms basically disappeared; ② Effective: Intraocular pressure decreased by 5-9 mmHg, central retinal artery blood flow perfusion improved (PSV and EDV increased by 10%-29%), optic ganglion cell layer thickness increased by 10%-19%, and clinical symptoms were alleviated; ③ Ineffective: Intraocular pressure decreased by <5 mmHg, central retinal artery blood flow perfusion and optic ganglion cell layer thickness did not improve, and clinical symptoms did not change significantly.

[0082] The treatment effects of each group were evaluated based on the above overall efficacy criteria, and the total effective rate was calculated.

[0083] Overall effectiveness rate = (Number of cases with significant effects + Number of cases with positive results) / Total number of cases × 100%

[0084] Table 4 Treatment efficacy in different groups

[0085] As shown in Table 4, the use of the traditional Chinese medicine product of this invention can effectively improve glaucoma. The number of cases with significant effect and the total effective rate are significantly higher than those of other comparative groups, and the effect is basically the same as that of the control group. (Four)

[0087] After treatment, patients in Example 4 group and the control group were followed up for 6 months. The recurrence rate of patients 6 months after the end of treatment was statistically analyzed. When the intraocular pressure of a patient increased by ≥21 mmHg again, it was determined to be a recurrence.

[0088] The results showed that the recurrence rate in group 4 was 2%, while the recurrence rate in the control group was 10%. The recurrence rate in group 4 was significantly lower than that in the control group, indicating that the optimized Chinese medicine components enhanced the liver and kidney nourishing and qi and blood regulating effects, strengthened eye resistance, and effectively reduced the recurrence rate.

[0089] In summary, the traditional Chinese medicine composition of this invention has a strong effect in lowering intraocular pressure, and can also improve retinal blood supply and prevent optic nerve atrophy caused by glaucoma. While achieving a dual improvement in efficacy and safety, it also reduces the recurrence rate and side effects. The technical solution of this invention also achieves a dual improvement in efficacy and safety, and reduces the recurrence rate and side effects.

[0090] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating glaucoma, characterized in that, The formula comprises the following components in parts by weight: 18-28 parts of cassia seed, 12-18 parts of wolfberry, 12-18 parts of cottongrass, 10-15 parts of vinegar-processed cyperus rhizome, 10-15 parts of mulberry leaf, 10-15 parts of chuanxiong rhizome, 8-12 parts of polyporus umbellatus, 5-8 parts of kudzu root, 5-8 parts of akebia stem, 3-5 parts of turmeric, 3-5 parts of indigo naturalis, and 2-4 parts of prepared licorice root.

2. The method for preparing the traditional Chinese medicine composition according to claim 1, characterized in that, Includes the following steps: (1) Crush cassia seed, wolfberry, vinegar-processed cyperus rhizome, mulberry leaf and roasted licorice root, mix them together, add water and decoct, filter to obtain filtrate 1; (2) After slicing Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata, mix them together, extract with ethanol, and filter to obtain filtrate 2; (3) Mix the obtained filtrate 1, filtrate 2, indigo with the crushed akebia and turmeric, and concentrate to obtain the final product.

3. The preparation method according to claim 1, characterized in that, After crushing in step (1), the material is sieved through a screen with a mesh size of 40-60.

4. The preparation method according to claim 1, characterized in that, The amount of water added in step (1) is 8-12 times the total mass of cassia seed, wolfberry, vinegar-processed cyperus rhizome, mulberry leaf, and roasted licorice root.

5. The preparation method according to claim 1, characterized in that, The decocting time in step (1) is 50-70 minutes per time, and the number of times the decocting is performed is 2-3 times.

6. The preparation method according to claim 1, characterized in that, In step (2), the volume-to-mass ratio of ethanol to the total mass of Eriocaulon buergerianum, Polyporus umbellatus, Ligusticum chuanxiong and Pueraria lobata is (10-20) mL:(1-3) g.

7. The preparation method according to claim 1, characterized in that, The extraction time in step (2) is 60-100 min / time, and the number of extractions is 2-3 times.

8. The use of the traditional Chinese medicine composition according to claim 1, or the traditional Chinese medicine composition prepared by any one of claims 2-7, in the preparation of drugs for treating glaucoma.

9. The application according to claim 8, characterized in that, The dosage forms of the medication for treating glaucoma include granules, capsules, or oral solutions.

Images